Neurological

Comparing the effectiveness and cost of levetiracetam and valproate in epilepsy

In patients with epilepsy, levetiracetam, which has been recommended as an alternative to valproate, especially for girls and women who may become pregnant, has not been clinically effective or inexpensive, according to study results published in The Lancet.

The Standard and New Antiepileptic Drug (SANAD) II study, an open-label, randomized, controlled phase 4 study, is the first randomized, controlled study to investigate these two measures for patients with newly diagnosed generalized or unclassified epilepsy were.

The study researchers conducted the study through the UK’s National Health Service Centers. This included adult and pediatric patients (aged 5 years or more) who had had at least 2 epileptic seizures in the past and who had never been treated with an antiseizure drug.

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The 520 patients had a mean age of 13.9 years and most were men or boys (65%). Most patients had generalized epilepsy (n = 397), including 104 with epilepsy without childhood. The other patients had unclassifiable epilepsies.

Study researchers randomly assigned patients 1: 1 to either the valproate or levetiracetam cohort and followed them for 2 years. The recommended daily dose for patients 5 to 12 years of age was 25 mg / kg valproate or 40 mg / kg levetiracetam. The recommended daily dose for patients over 12 years of age was 500 mg twice a day for valproate or levetiracetam.

The results showed that levetiracetam did not meet its definition of non-inferiority for the time to 12 months of remission from seizures (hazard ratio) [HR]1.19; 95% CI, 0.96-1.47; Non-inferiority margin, 1.314).

There was a 9% higher instant response rate after 12 months with valproate (26% versus 36%). The median time to achieve 12 month remission was shorter for valproate (445 days; 95% CI, 406-531) than for levetiracetam (636 days; 95% CI, 553-728), and per-protocol analysis showed improvement Remission with valproate as compared to levetiracetam.

The same applied to the time up to the 24-month remission with a difference of 12% and the time to the first attack (HR 0.82; 95% CI 0.67-1.00). The study researchers also found that levetiracetam was more likely to have poor seizure control (HR 0.43; 95% CI 0.30-0.63).

The total unadjusted cost was £ 61 higher for participants taking levetiracetam. Total adjusted cost for levetiracetam was £ 104 higher. Quality-adjusted life years (QALYs) were higher for valproate (1.637 QALYs; 95% CI, 1.565-1.673) than for levetiracetam (1.603 QALYs; 95% CI, 1.500-1.631) in the base case analysis.

Limitations of the study included the fact that some seizures might not have been reported, the open nature of the study, possible misclassification of patients, and the small number of participants classified with a particular generalized epilepsy syndrome.

When compared to valproate, levetiracetam was not found to be clinically effective or inexpensive. For girls and women of childbearing potential, these results provide discussions about the benefits and harms of avoiding valproate, ”concluded the study researchers.

Disclosure: Some authors of the study stated that they belong to the pharmaceutical industry. For a full list of the authors’ information, see the original reference.

References

Marson A., Burnside G., Appleton R. et al. The SANAD II Study of the Efficacy and Cost-Effectiveness of Valproate versus Levetiracetam in Newly Diagnosed Generalized and Unclassifiable Epilepsy: an open, multicentre, phase 4 study with no inferiority, randomized and controlled. Lancet. 2021; 397 (10282): 1375- 1386. doi: 10.1016 / S0140-6736 (21) 00246-4

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